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      Recent Advances in the Management of Cancer-Associated Thrombosis: New Hopes but New Challenges

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          Abstract

          Venous thromboembolism (VTE) is a common cause of morbidity and mortality in cancer patients and leads to a significant increase in health care costs. Cancer patients often suffer from multiple co-morbidities and have both a greater risk of VTE recurrence and bleeding compared to non-cancer patients. Anticoagulation is therefore challenging. For many years, long-term therapy with Low-Molecular-Weight Heparin (LMWH) was the standard of care for the management of cancer-associated VTE. Direct oral anticoagulants (DOAC), which offer the convenience of an oral administration and have a rapid onset of action, have recently been proposed as a new option in this setting. Head-to-head comparisons between DOAC and LMWHs for the treatment of established VTE are now available, and data on the efficacy and safety of these drugs for primary prophylaxis of VTE in ambulatory cancer patients receiving systemic anticancer therapy are emerging. This narrative review aims to summarize the main recent advances in the prevention and treatment of cancer-associated VTE, including recent data on the use of individualized factors to stratify the risk of VTE in each individual patient, quality-of-life in patients treated with LMWH, and the place that DOACs will likely take in the cancer-associated VTE management landscape.

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          Most cited references59

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          2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism.

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            Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer.

            Patients with cancer have a substantial risk of recurrent thrombosis despite the use of oral anticoagulant therapy. We compared the efficacy of a low-molecular-weight heparin with that of an oral anticoagulant agent in preventing recurrent thrombosis in patients with cancer. Patients with cancer who had acute, symptomatic proximal deep-vein thrombosis, pulmonary embolism, or both were randomly assigned to receive low-molecular-weight heparin (dalteparin) at a dose of 200 IU per kilogram of body weight subcutaneously once daily for five to seven days and a coumarin derivative for six months (target international normalized ratio, 2.5) or dalteparin alone for six months (200 IU per kilogram once daily for one month, followed by a daily dose of approximately 150 IU per kilogram for five months). During the six-month study period, 27 of 336 patients in the dalteparin group had recurrent venous thromboembolism, as compared with 53 of 336 patients in the oral-anticoagulant group (hazard ratio, 0.48; P=0.002). The probability of recurrent thromboembolism at six months was 17 percent in the oral-anticoagulant group and 9 percent in the dalteparin group. No significant difference between the dalteparin group and the oral-anticoagulant group was detected in the rate of major bleeding (6 percent and 4 percent, respectively) or any bleeding (14 percent and 19 percent, respectively). The mortality rate at six months was 39 percent in the dalteparin group and 41 percent in the oral-anticoagulant group. In patients with cancer and acute venous thromboembolism, dalteparin was more effective than an oral anticoagulant in reducing the risk of recurrent thromboembolism without increasing the risk of bleeding. Copyright 2003 Massachusetts Medical Society
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              Tinzaparin vs Warfarin for Treatment of Acute Venous Thromboembolism in Patients With Active Cancer: A Randomized Clinical Trial.

              Low-molecular-weight heparin is recommended over warfarin for the treatment of acute venous thromboembolism (VTE) in patients with active cancer largely based on results of a single, large trial.
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                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                10 January 2019
                January 2019
                : 11
                : 1
                : 71
                Affiliations
                [1 ]Institute of Cardiometabolism And Nutrition, INSERM UMRS_1166, Sorbonne Université, F-75013 Paris, France
                [2 ]Department of Haematology, Pitié-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris, F-75013 Paris, France
                [3 ]Autoimmune and Vascular Disease Unit, Internal Medicine (UF04), Center of reference for rare systemic autoimmne diseases (FAI2R), Saint-Louis Hospital, Assistance Publique Hôpitaux de Paris, F-75010 Paris, France; ilham.benzidia@ 123456aphp.fr (I.B.); dominique.farge-bancel@ 123456aphp.fr (D.F.)
                [4 ]Department of Haematology, Saint-Antoine Hospital, Assistance Publique Hôpitaux de Paris, F-75012 Paris, France; zora.marjanovic@ 123456aphp.fr
                [5 ]Department of Medicine, McGill University, Montreal, QC H3A 0E7, Canada
                Author notes
                [* ]Correspondence: corinne.frere@ 123456aphp.fr ; Tel.: +33-1-42-16-24-52
                Author information
                https://orcid.org/0000-0001-6303-4732
                https://orcid.org/0000-0003-2330-2290
                https://orcid.org/0000-0002-4041-1352
                Article
                cancers-11-00071
                10.3390/cancers11010071
                6357110
                30634638
                e0dcb5c7-c5b8-4fbe-b870-45762e4044d9
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 15 December 2018
                : 08 January 2019
                Categories
                Review

                venous thromboembolism,cancer,low molecular weight heparin,direct oral anticoagulant

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